The objective of the project is a quantitative evaluation of tumorigenesis of polycyclic aromatic hydrocarbons in relation to the extent of binding of these compounds to DNA. The biological systems elected for this study are the rat-liver nuclei and the mouse skin. The enzymic capacity of purified rat-liver nuclei to bind hydrocarbons to nuclear DNA is being pursued. The nature of the enzymes involved in metabolic activation will be investigated by comparing the binding of an aromatic hydrocarbon to DNA in relation to the aryl hydrocarbon hydroxylase and cytochrome P450 levels in nuclei and microsomes after previous enzymic induction of the liver with the same hydrocarbon. In addition, the skin and the purified liver nuclei will be used for the elucidation of the chemical nature of the DNA-benzo (a) pyrene bond. The isolated nucleoside-hydrocarbon after hydrolysis of the corresponding DNA will be compared with chemically synthesized known compounds. In this manner it is possible to establish which nucleic acid bases are involved in the binding and the chemical nature and position of the nucleoside-benzo (a) pyrene bond. The results should provide evidence of the mechanism of binding and define the significance of the interaction between hydrocarbon and DNA in the process of tumor initiation.